A COVID-19 Crash Course On Immunology
I know, I know…
You’re probably thinking that we’ve talked enough about how COVID-19 works already. You’re right. There’s already thousands of articles on the subject, and after all, nothing’s changed with how the disease works —
so why another one?
Well, the coronavirus has probably been the most amazingly uncomfortable thing we’ve experienced in at least the past couple of decades. But, what about the hundreds of epidemics and pandemics that we’ve had (and will) face in the near future?
More likely than not — the coronavirus isn’t going to be the last pandemic we see, but still — not many people know about how our bodies deal with diseases in general.
There might be thousands of articles around how COVID — 19 works, but not nearly as many as they should be surrounding how a viral disease even works.
That’s why I decided to write this article — to inform everyone about the much wider field of immunology outside of the coronavirus, so that we as a society can stay aware of any disease we might end up facing down the road.
Macrophages: Your First Line Of Defense
Before we start an adventure through our absolutely fascinating immune system, lets set up an imaginary scenario: you’re working and accidentally get a nasty paper cut — nothing serious, but still pretty unpleasant. Now there’s an opening in your skin, and to bacteria, that’s the equivalent of a “Come In, We’re Open!” sign.
Unfortunately, a bacteria called staphylococcus (better known as staph) was waiting for this opportunity around the corner.
So, without too much effort, the staph bacteria enter the recently formed cut, use your own energy to start replicating exponentially, and eventually, could start doing some serious damage to your body.
In immunology, any foreign substance that provokes our immune system is known as an antigen. But antigens aren’t just limited to bacteria and viruses — they could be organs that our bodies reject after getting them replaced, pacemakers, or for people with allergies, they could be gluten, peanuts, or basically anything in between:
But don’t fear — our body has some of the most advanced front line defence of any species, and they’re called macrophages. In Greek, they literally translate to ‘big eaters’, and that’s exactly what they’re best at. Our macrophages are about 21 micrometres in size — a bit less than the width of a human hair, but that doesn’t seem to stop them from having a huge appetite, with a limit of over 100 bacteria each!
These cells eat up as many pathogens as they can (I wish I could eat for a living), but here’s the cool part — when they’re done, the digestive acid inside of them burns the antigens to death, and in most cases, your macrophages alone should be able to gobble up most of the staph that entered your body.
Dendritic Cells: The Brains
So, what happens if your macrophages weren’t enough to get rid of an antigen? If the staph bacteria continues to spread, then that could be really bad news.
That’s exactly where your dendritic cells come into play, and what they do is pretty simple. When your macrophages send signals to your dendritic cells, they get engaged, and as soon as that happens, they try and find out whether the antigen is a bacteria or virus. In this case though, the dendritic cell knows that it’s dealing with the staph bacteria, so it gets right to work by taking samples from the antigen.
But why does it do that?
Because the parts of the bacteria can be identified by other immune cells! Any cell that has a nucleus also has a molecule on its surface, known as the major histocompatibility complex (MHC), which allows it to display shards of antigens on their surface. In around a day, it travels all the way to the nearest lymph node in your body, where millions of T-Cells are waiting to recognize the issue.
T-Cells : The Brawn
You’ve probably heard of T-Cells before — they’re the immune cells designed to defend our body from (almost) any antigen we would ever encounter.
To be more specific, T-Cells fall into the category of white blood cells, along with the B-Cells I’ll go on to cover soon, but together, both T and B-Cells from what we call lymphocytes:
For now, just know that there’s three major types of T-Cells — helper, Killer (Cytotoxic), and Suppressor T-Cells, and each one plays an important role in keeping our immune system in top shape. For the most part, helper Ts have the ability to activate other immune cells by releasing potent compounds called cytokines.
On the other hand, Killer Ts do exactly what their name says — they kill. Each Killer T-Cell is equipped with a unique set of receptors, and each receptor can bind to a specific antigen. The system’s like a jigsaw puzzle of sorts, and the better the fit, the easier the T-Cell can destroy its target.
And last (but certainly not the least) come the Suppressor Ts. If it weren’t for them, then we would be almost guaranteed to have our own T-Cells attack us from the inside-out. Suppressor T-Cells know when the fight against an antigen is over, and let Killer Ts know its time to calm down, to prevent them from causing harm to us.
** Quick Note: T-Cells can function both when you have an outside antigen (eg. the flu, staph, etc.) or when our own cells start functioning poorly (eg. cancer). For the purposes of this crash course, I’ll be referring to how T-Cells respond to external antigens**
Let’s go back to the staph antigens that invaded your body after you got a horrible paper cut. Not long after, a Killer T-Cell that has a matching receptor binds to it, but what next?
Now here comes the really stunning part — when the T-Cell binds perfectly with an antigen, it gets activated:
The activation of a T-Cell results in an entire cascade of events. Since the T-Cell successfully bound to a foreign substance, it replicates, because there’s going to be a lot more of where that bacteria came from.
On top of that, the T-Cell releases proteins that act as mini-bullets — punching through the membrane of the foreign cell and killing it almost instantly.
Wait, but how do T-Cells do all this?
You Think Harvard Is Selective?
Well, the answer to that seemingly short and simple question comes with a surprisingly long answer — after all, our bodies are some of the most complex machines we know. So, for more context, here’s a story of a T-Cell’s life:
- All T-Cells are formed form a common precursor or ancestor. They’re called hematopoietic stem cells. These stem cells can differentiate (transform) into a variety of different cells, and they’re formed in your bone marrow.
2. These “baby T-cells” don’t know how to target any disease yet, since they haven’t developed any receptors yet. Do do this, the cells need to travel to a little immune organ sitting just above your heart, called the thymus gland:
3. To attract all the T-Cells hanging around in your bone marrow, the thymus does something really fascinating. Through a process called chemotaxis, it releases chemicals that lead the immune cells to where they need to be.
4. Now that the T-Cells have gotten to the thymus, it’s time to transform them into antigen killing machines! You can think of the thymus as a university on steroids, and the cells in your thymus (thymic cells) as some hardcore teachers.
5. First, the thymic cells release compounds called recombinases into the freshman T-Cells that shuffle up their DNA. This process is arguably the most important since before, all the T-Cells shared the same genes. That means that they could only fend off one disease, and recombination lets them produce millions of different receptors for different diseases.
6. Along with their newly formed T-Cell Receptors (TCRs), our sophomore T-Cells also receive two proteins called CD4 and CD8, and the thymic cells text out whether these proteins can properly bind to them. If the T-Cells don’t bind as they should, then the thymic cells just kill them off (pretty harsh punishment for failing a test).
7. For the junior-year cells that passed the test, it’s just about time for another one — autoimmunity! The (still really strict) thymic cells test the immune cells for whether they would bind to cells in our own bodies. If they do, that could lead to some life-threatening autoimmune diseases like multiple sclerosis. And again, the unlucky T-Cells that fail are killed off.
8. And finally, for the senior T-Cells that somehow found a way to survive the wrath of the thymic cells, it’s time for a turning point in their lives — think of this as graduation. Remember the CD4 and CD8 proteins I mentioned earlier? Well, in a relatively random process, these cells become helper, killer (cytotoxic), or suppressor T-Cells depending on how their CD proteins interacted with the thymic cells:
9. Now that they’re graduated, it’s time for the T-Cells to move on and get a job somewhere inside our bodies — that could stay in our thymus, our lymph nodes, or even around our spleen, all waiting to neutralize their next antigen.
The bottom line is that the entire training process for immune cells can be gruelling. Only around 1% of original T-Cells that came in end up surviving “thymus university”— now that’s a selective school!
B-Cells And Their Antibodies
And now, for another vital cell in our immune system — B-Cells! Don’t worry though — I’m not going to be taking you through the same long explanation that I did for T-Cells since they’re similar in a lot of ways. B-Cells get trained in almost the same way and come in essentially the same forms as T-Cells do, but let’s cover the differences:
Unlike T-Cells with their receptors, B-Cells have a set of unique proteins called antibodies attached around their membrane (call them immunoglobulins if you want to sound smart), and they can be the difference between you thinking of a papercut as an inconvenience, or a time to start worrying about dying from a fatal infection:
Just like T-Cells, every B-Cell has thousands of a specific antibody on its membrane, with each one having a fixed portion at its base, and a unique geometry of compounds at its end.
On the other hand, B-Cells go through a similar recombination process that T-Cells go through, which is what allowed those cells that had identical DNA to produce almost 10 BILLION possible combinations of antibodies on their surface.
And the similarities don’t end there — B-Cells can be activated just like T-Cells can, but they need a little help. When a B-Cell and a helper T-Cell with matching proteins meet, it activates the cell. In this case though, a B-Cell being activated has slightly different outcomes. Of course, the B-Cell multiplies rapidly, but it also creates two new cell types in the process — memory cells and effector cells.
Memory B-Cells are pretty unique — the activated B-Cell produces it to help create long-lasting immunity for us, so when that same virus comes back, you’re already immune to it since you have B-Cells to detect them. That’s a major reason why you don’t get diseases like chicken-pox more than once, since your body has already created memory B-Cells to keep it in check if it comes back:
Vaccines leverage the same principle — they introduce a less potent form of a virus into your system, that your immune system can easily fight it off, but it allows your body to create memory B and T-Cells for future encounters with the same virus.
On the other hand, effector B-Cells (plasma cells) are like mini antibody-factories — producing the same antibodies belonging to the originally activated cell, but this time, they aren’t bound to the cell’s membrane. This time, the antibodies rush towards the antigen rather than the other way around:
Does that ring a bell? If you’ve heard of some of the many experimental therapies being tested for COVID-19, plasma replacement would be one of them. By extracting the plasma cells from the blood of a recovered patient and transferring it into a newly diagnosed one, we can (theoretically) assist their immune systems in fighting off the virus.
But, would a simple antibody even do any damage to antigens?
Well, not really. Antibodies don’t directly harm anything — they play a much more complicated role in destroying antigens, and they can achieve that in two major forms — blocking and tagging.
Back to the example of the staph bacteria:
when an antibody binds to the bacteria’s surface (epitope), it makes it that much harder for the antigen to continue infecting you, since they can only function through binding to your cells, and antibodies prevent that from happening.
Another (more peculiar) way antibodies help eliminate antigens is by acting as “Hey, Eat This!” signals to cells like your macrophages. As I mentioned earlier, these cells have enormous appetites, and with the help of your antibodies, they can wreak some massive havoc on the staph antigens that decided to call your body home.
And when it comes to the imaginary staph bacteria that entered you body — it didn’t even stand a chance. With the millions of immune cells and mechanisms in you, their fate was sealed ever since they entered. After all, it wouldn’t be too convenient to be bedridden after getting scratch on your finger, would it?
Our immune systems are the result of eons of evolution — all coming together to create one of the most effective natural machines we know. So, in the grand scheme of the fascinating biological systems that we are, this article hasn’t even started to delve into all the little complexities of just a singular field that goes into making humans, humans.
I think that the sheer intricacy of it all is something we tend to forget— especially in a time like this, when we feel like we’re nothing against a virus. And hopefully, we’ll all start to remember that we’re a lot stronger than we think we are.
Thanks for reading, and stay safe,